The renal sensitivity for endogenous parathormone in patients with primary hyperparathyroidism, vitamin D deficiency and renal stones

Baseline levels and increases in urinary cyclic AMP excretion (UcAMP) and immunoreactive parathormone (iPTH) were studied before and during infusion of EDTA in euparathyroid patients with renal stones (n=11), patients with primary hyperparathyroidism (PHP; n=14) and patients with vitamin D deficiency (n = 12). In all three groups, EDTA evoked a significant rise in iPTH and UcAMP. In patients with PHP and in those with vitamin D deficiency, there was a sufficiently close relationship between increments in iPTH (delta iPTH) and in UcAMP (delta UcAMP) (r = 0.90, P less than 0.001 and r = 0.67, P less than 0.02, respectively) to use this model to assess renal sensitivity for changes to endogenous PTH levels. We quantified sensitivity of the kidney for PTH, by calculating the ratio delta UcAMP/delta TPTH for the three studied groups. The ratio was comparable in patients with renal stones (16.7 +/- 10.3) and PHP (13.8 +/- 4.9, P greater than 0.10), but was significantly increased in patients with vitamin D deficiency (33.2 +/- 17.9; P less than 0.01 versus patients with renal stones and P less than 0.01 versus patients with PHP). Within the group of patients with PHP there was no correlation between baseline serum calcium concentrations and the ratio delta UcAMP/delta TPTH. It is concluded that in patients with vitamin D deficiency, renal sensitivity to PTH is increased compared with patients with PHP and euparathyroid patients with renal stones, perhaps an expression of a teleological useful adaptation of end organ sensitivity.     

A radioimmunoassay for the measurement of aminopeptidase (microsomal) in human serum

A radioimmunoassay for the measurement of aminopeptidase (microsomal) (AP) in human serum was developed by using antiserum to human kidney AP. AP purified from kidney and AP present in normal serum and in serum from a patient with obstructive jaundice gave parallel logit-log transformation lines, suggesting immunological identity. The mean concentration of AP in normal serum (n = 104) was 1.33 +/- 0.30 (mean +/- SD) micrograms/ml. Men had significantly higher serum AP levels (1.41 +/- 0.30 micrograms/ml) (p less than 0.005) than women (1.24 +/- 0.28 micrograms/ml). Serum AP levels of patients with hepatoma (2.26 +/- 0.87 micrograms/ml) and cancer of the pancreas or the biliary tract (2.90 +/- 0.67 micrograms/ml) were significantly higher (p less than 0.005) than those of normal subjects. Patients with acute and chronic hepatitis (2.06 +/- 0.66 micrograms/ml) also had significantly higher serum AP levels (p less than 0.005) than normal subjects. In pregnant women, however, the increase in AP activity without the increase in AP concentration showed that the increased AP activity was due to an enzyme other than AP. The enzyme levels and activities in normal serum as well as in patients' sera were significantly correlated (normal, r = 0.77; patients, r = 0.95). Based on the specific activity of AP purified from human plasma, the enzyme activity splitting L-alanyl-beta-naphthylamide is due almost completely to AP in normal subjects and in patients with hepatobiliary diseases.     

Nutrition and somatomedin. XIX. Molecular regulation of insulin-like growth factor-1 in streptozotocin-diabetic rats

Poor growth in diabetes involves low circulating levels of somatomedins/insulin-like growth factors (IGFs), largely reflecting decreased growth factor release by the liver. To define regulatory mechanisms, circulating IGF-1 was compared with levels of a high mol wt putative hepatic IGF-1 precursor and hepatic IGF-1 mRNA in a model of progressive severity of diabetes in rats. Streptozotocin administered at 36, 72, 144, and 288 mg/kg produced graded metabolic decompensation 2 days later, from minimal hyperglycemia with continued weight gain at 36 mg/kg, to marked hyperglycemia, ketonemia, and weight loss at 288 mg/kg (all P less than 0.001). Total serum IGF-1 measured by RIA was unchanged with the 36 and 72 mg/kg doses of streptozotocin (471 +/- 19 and 439 +/- 27 ng/ml, respectively, vs. 517 +/- 27 ng/ml in controls) despite serum glucose greater than 400 mg/dl. With streptozotocin 144 and 288 mg/kg, serum IGF-1 fell to 131 +/- 27 and 142 +/- 10 ng/ml, respectively (both P less than 0.005 vs. controls). Serum IGF-1 was correlated strongly with serum beta-hydroxybutyrate and body weight (r = -0.88 and 0.91, respectively, P less than 0.0001), and less strongly with serum glucose (r = -0.59, P less than 0.0002). Extractable hepatic content of a high mol wt form of immunoreactive IGF-1 (a putative precursor) was unchanged at the two lowest doses of streptozotocin (68 +/- 4 and 83 +/- 9 ngeq/g vs. 67 +/- 4 in controls), but decreased to 16 +/- 3 and 29 +/- 4 ng/g at the two highest doses (both P less than 0.001 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of age and sex in serum osteocalcin levels in thoroughbred horses.

In this study, we assessed the potential value of free serum osteocalcin or bone gla protein (BGP), the most abundant non collagenous matrix protein found in bone and dentin, to reflect changes of bone turnover in thoroughbred horses. Levels of osteocalcin were analyzed in serum samples of 54 clinically normal animals divided into three groups (A, B, C) according to age: 8, 16-18 and 24-36 months, in order to determine the standard for young horses of different age and sex. Serum BGP was measured by an in-house developed double antibody radioimmunoassay using bovine antigen. The mean BGP levels (ng/ml) were 45.65 +/- 11.69; 33.65 +/- 16.65; 15.08 +/- 6.70 respectively for groups A, B and C; statistically significant differences were found between groups (A vs B and C; Bvs C). Difference between males and females was found significant in group C with higher values in the females: 18.75 +/- 5.00 against 14.43 +/- 10.47 i n the males. This can be considered a sex related effect on BGP serum levels after the onset of puberty. Correlation coefficient between age and serum BGP for females and males were r 5 20.598 ( P < 0.001) and r 5 200.807 (P < 0.001) respectively. A significant negative linear relationship could be established between these two parameters in males during the growth period. The regression equation between serum BGP and age for males was (month of age = 65.14-1.68. BGP). In the female group the gestation and lactation are variables that lower the correlation coefficient between age and serum BGP levels. These results suggest that serum BGP decreases in thoroughbred horses during the growth period, and significant differences between sexes were found only after the onset of puberty.     

The relationship of serum vitamin A, cholesterol, and triglycerides to the incidence of ovarian cancer

Prospective and retrospective studies have suggested that serum vitamin A and total cholesterol levels may be associated with cancer. Our study showed that the mean (+/- SEM) concentrations of serum vitamin A 489 +/- 33.28 (mean +/- SEM micrograms/liter and serum total cholesterol 174.7 +/- 8.96 (mean +/- SEM) mg/dl from ovarian cancer patients in Singapore were significantly lower than the respective values of 668 +/- 25.10 (mean +/- SEM) microgram/liter and 210.7 4.48 (mean +/- SEM) mg/dl from noncancerous control subjects (P less than 0.0001 for both compounds). In addition, ovarian cancer patients did not show significantly lower serum triglyceride levels than the control subjects. Age did not significantly correlate the serum vitamin A and total cholesterol concentrations, but there was correlation with respect to the serum triglyceride levels. There were moderate correlations between vitamin A and cholesterol levels (r = 0.36, P less than 0.0027) and between cholesterol and triglyceride levels (r = 0.37, P less than 0.0024) in the control subjects but not in the cancer patients. Vitamin A levels correlated moderately with triglyceride levels in both the cancer patients (r = 0.42, P less than 0.0258) and the control subjects (r = 0.33, P less than 0.0069). The inverse relationship between the incidence of ovarian cancer and serum vitamin A and serum total cholesterol concentrations may have distinct implications for preventive medicine and public health.     

Serum and urine chromium as indices of chromium status in tannery workers

Serum and urinary Cr levels of a selected group of men exposed to CrIII in four Southern Ontario tanneries were compared with those of men not exposed to Cr. Fasted blood samples were obtained from 72 tannery workers (TW; mean age +/- SD = 36 +/- 12 years) and from 52 controls (CS; mean age +/- SD = 41 +/- 13 years). Serum Cr levels as determined by graphite furnace atomic absorption spectrophotometry were significantly higher (P = 0.0001) for TW (median 0.49 ng/ml, range 0.37-0.81) than for CS (median 0.15 ng/ml, range 0.12-0.20). Urine samples were collected from 49 TW and 43 CS on a Friday pm and from 42 TW on a Monday am. Urinary creatine (Cre) was determined by the Jaffe reaction. For Friday samples, the median urinary Cr/Cre ratio was significantly higher (P = 0.0001) for TW (median 0.83 ng/mg, range 0.48-1.82) than for CS (median 0.18 ng/mg, range 0.13-0.26). For TW, Cr/Cre was correlated with serum Cr (r = 0.72, P = 0.0001). Neither urinary Cr/Cre nor serum Cr was correlated with length of employment in the tanning industry. There were significant differences in serum Cr levels and urinary Cr/Cre ratios among TW employed in different areas of the tanneries. For TW, the median urinary Cr/Cre ratio for Monday morning samples was significantly lower than for Friday afternoon samples (P = 0.03). These data indicate that CrIII is absorbed and that serum and urine Cr in tannery workers may be indices of Cr exposure and status.     

Effect of estrogens on renal responsiveness to parathyroid hormone in elderly female subjects

The effect of estrogens on the renal responsiveness to parathyroid hormone (PTH) was examined by PTH loading tests with synthetic human-PTH (1-34) in 8 normal elderly females (mean +/- SD age, 81.0 +/- 7.1 yr) before and after administration of estrogen (Premarin 1.25 mg/day for 4 weeks). Basal urinary adenosine cyclic 3', 5'-monophosphate (cAMP) excretion showed a tendency to increase after estrogen administration (5.47 +/- 1.68 vs 6.60 +/- 2.67 nmol/100 ml GFR) and the theoretical renal phosphorous threshold showed a tendency to decrease from 3.22 +/- 0.98 to 2.73 +/- 0.56 mg/dl. The blood ionized calcium concentration did not change after estrogen administration (4.44 +/- 0.16 vs 4.32 +/- 0.20 mg/dl) and serum phosphorous (P) decreased significantly (3.65 +/- 0.47 vs 3.01 +/- 0.42 mg/dl, p less than 0.05). There was no increase in mean serum immunoreactive PTH (0.34 +/- 0.10 vs 0.34 +/- 0.05 ngeq/ml). The urinary excretions of cAMP in response to PTH loading [100 U of human-PTH (1-34), intravenously] significantly (p less than 0.05) increased (94.8 +/- 57.0 vs 196.7 +/- 118.3 nmol/100 ml GFR/h) after estrogen administration. Moreover the changes in urinary excretion of cAMP (r = 0.698, p less than 0.01) and P (r = 0.555, p less than 0.05) induced by the PTH loading were positively correlated with serum estradiol in elderly females, assessed as groups before and after estrogen administration. These results suggest that estrogens may enhance the renal responsiveness to exogenous PTH administration.     

Characterization of obese women with reduced sex hormone-binding globulin concentrations

Factors influencing sex-hormone binding globulin (SHBG) concentrations in obesity are poorly understood. Preliminary observations suggest that dietary lipids may be involved and there are data confirming a direct inhibiting effect of insulin. Since only some obese subjects show lowered SHBG levels, we performed this study with the aim of defining obese women with low SHBG (LSO) (2 SD above normal values) in comparison with those presenting normal globulin concentrations (NSO). These groups were selected from a larger group of obese women with a history of normal menses and aged less than 40 years. An age-matched group of normal weight healthy women served as controls. Both LSO and NSO had similar body mass index and percentage body fat, but the waist to hip girth ratio (WHR), an index of body fat distribution, was significantly higher in LSO (0.88 +/- 0.04) than in NSO (0.81 +/- 0.09; P less than 0.05). Gonadotropin and androgen concentrations were similar in both groups, whereas estrone (E1) levels were higher in LSO (32.8 +/- 15.8 pg/ml) than in NSO (19.4 +/- 6.2 pg/ml; P less than 0.05; controls: 23.5 +/- 7.8 pg/ml; P less than 0.05). Moreover, compared to NSO, LSO women had significantly higher glucose-stimulated insulin and C-peptide levels. Partial regression analysis revealed significant correlation coefficients between SHBG, stimulated insulin values (r = -0.38; P less than 0.05) and WHR (r = 0.40; P less than 0.005). Therefore, compared to NSO, LSO women have distinctive clinical and endocrine characteristics, namely more pronounced hyperinsulinemia, higher E1 concentrations and a central type body fat distribution.     

Effects of age, sex and renal function on urinary insulin-like growth factor I (IGF-I) levels in adults.

Insulin-like growth factor I (IGF-I) levels in urine were measured in adults using specific RIA after extraction with acid-ammonium sulfate. Mean (+/- SD) total urine IGF-I values were 267.9 +/- 112.9 ng/day and 167.8 +/- 73.2 ng/g creatinine (Cr) in 17 normal young adults. There was a positive correlation (r = 0.785, P < 0.001) between IGF-I values in early morning urine and those of 24 h urine when they were corrected by urinary Cr. IGF-I values in early morning urine were ranged from 60 to 1,100 ng/gCr with a mean value of 309.6 ng/gCr in 178 normal adults aged 21-80 yr. There was a consistent trend towards higher urinary IGF-I values in males during aging and this trend did not reach statistical significance until the sixth and seventh decades. There was a positive correlation (r = 0.465, P < 0.005) between urinary IGF-I values and age in males but not in females. Although urinary IGF-I values were higher in females than in males of the second and third decades, no sex difference was found in older adults. Urinary IGF-I values were correlated reversely with 24 h Cr clearance (CCr) and positively with urinary beta 2-microglobulin (beta 2-MG) levels in patients with renal dysfunction. These findings indicate that urinary IGF-I levels are influenced by age, sex and renal function in adults.     

Serum aldosterone and protein-binding variables in Yanomama Indians: a no-salt culture as compared to partially acculturated Guaymi Indians

Yanomama Indians from the jungles of southern Venezuela and northern Brazil excreted 1 +/- 1.5 mEq of Na and 203 +/- 109 mEq of K and had low blood pressure (BP), 102/62 mm Hg). In comparison, Guaymi Indians of Panama excreted 103 +/- 50 mEq of Na and 118 +/- 52 mEq of K and had significantly higher BP (114/75 mm Hg, p less than 0.001). Elucidating the renin-aldosterone axis, total upright serum aldosterone in 34 Yanomama was high (85.6 +/- 78 ng/100 ml). The binding capacities of thermolabile (ABG) and thermostable (ABG-Ts) serum globulins for aldosterone were elevated at 23.8 +/- 6 and 14.9 +/- 2.6%, respectively; consequently, total ABG- plus ABG-Ts- bound aldosterone was as high as 38.6 +/- 6.3%. Plasma renin activity (PRA 10.3 +/- 2.4 ng/ml/h) and urinary aldosterone 18-glucuronide (70.3 +/- 30 micrograms/24 h) in 17 Yanomama were also very high. In contrast, total serum corticosteroids and corticosteroid-binding globulin (CBG) binding capacity were normal, suggesting normal ACTH activity. PRA correlated positively with total (r = 0.47, p less than 0.05) and free (r = 0.47, p less than 0.05) serum aldosterone, which in turn showed a negative trend with Na (r = 0.33, NS) excretion. The effect of high dietary K appeared less important to aldosterone stimulation and PRA suppression. ABG-bound aldosterone (r = 0.43, p less than 0.01) as well as ABG-Ts (r = 0.56, p less than 0.05) were negatively correlated with diastolic but not systolic BP. The total ABG- and ABG-Ts-bound fraction correlated with diastolic BP (r = 0.43, p less than 0.05) in contrast to the free fraction (r = 0.08, NS) or total aldosterone (r = -0.09). Apparently, only bound serum aldosterone is important for the maintenance of diastolic BP. High serum aldosterone, with elevated excretion, indicates an increased secretion rate; increased serum protein binding suggests an increased tissular activity and alterations in aldosterone metabolism. In Guaymi Indians both total plasma aldosterone (14.5 +/- 65 ng/100 ml) and urinary aldosterone (8.1 +/- 4.8 micrograms/creatinine excretion) were normal. ABG-binding capacity for aldosterone was moderately elevated (17.8 +/- 4.8) and of ABG-Ts normal (10.2 +/- 1.2) suggesting a nearly normal aldosterone metabolism and regulation. The BP of Guaymi was significantly higher than that of the Yanomama.     

Influence of thyroid function on serum bone Gla protein

The serum BGP level was assayed in patients with hyperthyroidism (untreated and remittent cases) and hypothyroidism. The mean serum BGP concentration was 9.7 +/- 0.90 ng/ml in 30 patients with untreated hyperthyroidism which was significantly higher than the 2.7 +/- 0.38 ng/ml in 15 remittent patients and 1.3 +/- 0.31 ng/ml in 13 patients with hypothyroidism (p less than 0.001, p less than 0.001). Serum BGP had a significant positive correlation with the concentrations of free triiodothyronine and alkaline phosphatase in the serum, while it had a significant negative correlation with serum PTH. In the patients with hypothyroidism, serum BGP increased significantly in parallel with increases in serum free triiodothyronine with thyroxine therapy. In the patients with hyperthyroidism, serum free triiodothyronine decreased significantly after the first month of methimazole treatment, and fluctuated within the normal range after two months. Serum alkaline phosphatase and BGP did not show significant changes during the first six months of treatment, although they were eventually reduced significantly at the end of one year. These results suggest that thyroid hormone directly stimulates the synthesis and secretion of BGP in existent osteoblasts and also acts on the bone remodeling cycle, therapy accelerating the rate of bone formation; the latter action may occur over a long period.     

Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction

Endoglin is a proliferation-associated and hypoxia-inducible protein expressed in endothelial cells. The levels of soluble circulating endoglin and their prognostic significance in patients with acute myocardial infarction (AMI) are not known. In this observational prospective study serum endoglin levels were measured by ELISA in 183 AMI patients upon admission to hospital and 48 hrs later and in 72 healthy controls. Endoglin levels in AMI patients on admission were significantly lower than in healthy controls (4.25 +/- 0.99 ng/ml versus 4.59 +/- 0.87 ng/ml; P= 0.013), and decreased further in the first 48 hours (3.65 +/- 0.76 ng/ml, P < 0.001). Upon follow-up (median 319 days), patients who died had a significantly greater decrease in serum endoglin level over the first 48 hrs than those who survived (1.03 +/- 0.91 versus 0.54 +/- 0.55 ng/ml; P= 0.025). Endoglin decrease was an independent predictor of short-term (30 days) (hazard ratio 2.33;95% CI = 1.27-4.23; P= 0.006) cardiovascular mortality, and also predicts overall cardiovascular mortality during the follow-up (median 319 days) in AMI patients (hazard ratio 2.13;95% CI = 1.20-3.78; P= 0.01). In conclusion, early changes in serum endoglin may predict mortality after AMI.     

Effects of calcitonin gene-related peptide on renal blood flow in the rat

The effects of alpha-rat calcitonin gene-related peptide (alpha-rCGRP) on systemic and renal hemodynamics and on renal electrolyte excretion were examined in normal anesthetized rats. In one group of rats (n = 7), infusions of alpha-rCGRP at doses of 10, 50, 100, and 500 ng/kg/min for 15 min each produced dose-related and significant decreases in mean arterial pressure from a control of 130 +/- 3 mm Hg to a maximal depressor response of 91 +/- 2 mm Hg. During the first three doses of alpha-rCGRP, renal blood flow progressively and significantly increased from a control of 5.0 +/- 0.3 ml/min to a peak level of 6.3 +/- 0.3 ml/min achieved during the 100 ng/kg/min infusion. With the highest infusion rate of 500 ng/kg/min, renal blood flow fell below the control level to 4.5 +/- 0.2 ml/min (P less than 0.05). The responses in renal blood flow and mean arterial pressure were associated with reductions in renal vascular resistance. After cessation of alpha-rCGRP infusions, arterial pressure, renal blood flow, and renal vascular resistance gradually returned toward the baseline values. In another group of rats (n = 9), infusion of alpha-rCGRP for 30 min at 100 ng/kg/min produced a significant reduction in urinary sodium excretion from 0.28 +/- 0.06 to 0.14 +/- 0.5 muEq/min (P less than 0.05). Urine flow and urinary potassium excretion also appeared to decrease, but the changes were not significantly different (P greater than 0.05) from their respective baselines. These results demonstrate that alpha-rCGRP is a potent and reversible hypotensive and renal vasodilatory agent in the anesthetized rat. The data also suggest that alpha-rCGRP may have significant effects on the excretory function of the kidney.     

The source of urinary epidermal growth factor in humans

To clarify the source of human urine EGF, we studied EGF renal clearance in 20 healthy, young adult subjects. Immunoreactive EGF was measured hourly in EDTA plasma, heparin plasma, serum and urine of 12 males and 8 females during a 3 h study period. Plasma and urine creatinine and creatinine clearance were measured and calculated hourly. Mean (and SEM) creatinine clearance was similar in males and females (118 +/- 12 vs 105 +/- 6 ml/min). EGF was not detectable in plasma, whereas relatively high levels were measured in serum (2.5 +/- 0.25 vs 1.5 +/- 0.18 ng/ml in males and females respectively p less than 0.05). Urine EGF excretion averaged 1641 +/- 233 ng/h in males and 1507 +/- 191 ng/h in females (p greater than 0.05). A significant correlation was observed between urine creatinine and urine EGF concentrations in both male (r = 0.98, p less than 0.01) and female (r = 0.94, p less than 0.01) subjects. EGF immunoreactivity in urine and serum eluted from G-75 sephadex columns similarly to recombinant 6000 Mr hEGF. Urine excretion of EGF approximated 1.5 micrograms/h or 25 ng/mg creatine. The high concentrations of EGF found in urine in the face of non-detectable levels of EGF in plasma favor the hypothesis that EGF in urine is derived from kidney synthesis and secretion. The significant positive correlation between urine creatinine and urine EGF suggests a functional correlation between glomerular filtration and the process of tubular EGF excretion.     

Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects

To understand the day-to-day pathophysiology of impaired muscle glycogen storage in type 2 diabetes, glycogen concentrations were measured before and after the consumption of sequential mixed meals (breakfast: 190.5 g carbohydrate, 41.0 g fat, 28.8 g protein, 1253 kcal; lunch: 203.3 g carbohydrate, 48.1 g fat, 44.0 g protein, 1497.5 kcal) by use of natural abundance (13)C magnetic resonance spectroscopy. Subjects with diet-controlled type 2 diabetes (n = 9) and age- and body mass index-matched nondiabetic controls (n = 9) were studied. Mean fasting gastrocnemius glycogen concentration was significantly lower in the diabetic group (57.1 +/- 3.6 vs. 68.9 +/- 4.1 mmol/l; P < 0.05). After the first meal, mean glycogen concentration in the control group rose significantly from basal (97.1 +/- 7.0 mmol/l at 240 min; P = 0.005). After the second meal, the high level of muscle glycogen concentration in the control group was maintained, with a further rise to 108.0 +/- 11.6 mmol/l by 480 min. In the diabetic group, the postprandial rise was markedly lower than that of the control group (65.9 +/- 5.2 mmol/l at 240 min, P < 0.005, and 70.8 +/- 6.7 mmol/l at 480 min, P = 0.01) despite considerably greater serum insulin levels (752.0 +/- 109.0 vs. 372.3 +/- 78.2 pmol/l at 300 min, P = 0.013). This was associated with a significantly greater postprandial hyperglycemia (10.8 +/- 1.3 vs. 5.3 +/- 0.2 mmol/l at 240 min, P < 0.005). Basal muscle glycogen concentration correlated inversely with fasting blood glucose (r = -0.55, P < 0.02) and fasting serum insulin (r = -0.57, P < 0.02). The increment in muscle glycogen correlated with initial increment in serum insulin only in the control group (r = 0.87, P < 0.002). This study quantitates for the first time the subnormal basal muscle glycogen concentration and the inadequate glycogen storage after meals in type 2 diabetes.     

A sandwich enzyme-linked immunosorbent assay for human plasma apolipoprotein A-V concentration

Apolipoprotein A-V (apoA-V) is a recently discovered apolipoprotein that appears to have a role in plasma triglyceride (TG) transport. We have developed an ELISA for apoA-V using monoclonal antibodies that has a lower limit of detection of 0.3 ng/ml and linearity up to 20 ng/ml. The ELISA was then used to quantify plasma apoA-V in 196 healthy subjects and 106 patients with insulin-resistant diabetes mellitus. In the healthy subjects, total apoA-V concentration was 179.2 +/- 74.8 ng/ml, and it was greater in females than in males (P < 0.005). It was correlated positively with the plasma HDL cholesterol (r = 0.32, P < 0.0001), apoA-I (r = 0.27, P = 0.0001), and apoE (r = 0.18, P = 0.011) concentrations and negatively with plasma TG concentration (r = -0.22, P = 0.021). In relation to single nucleotide polymorphism 3 (-1131C/T) of the apoA-V gene, apoA-V concentration was higher in the T/T type than in the C/C type (P < 0.01). Plasma TG concentration was lower in the T/T type than in the C/C or C/T type (P < 0.05). ApoA-V concentration was lower in the diabetic patients (69.4 +/- 44.3 ng/ml; P < 0.01) than in the healthy controls.     

Reduced plasma lipoprotein lipase activity in patients with malignancy-associated weight loss

Post-heparin plasma lipoprotein lipase activity was measured in 28 cancer patients with varying degrees of weight loss, and in 16 normal volunteers. Total lipoprotein lipase activity was decreased by 35.4% (P less than 0.001) in the cancer group. The component lipase activities, hepatic (HLPL), and peripheral (PLPL), were decreased by 40% (P less than 0.001) and 38% (P less than 0.005) respectively. In addition, the level of total peripheral lipoprotein lipase correlated well with the percent body weight lost by these patients (r = 0.6, P less than 0.01). Regardless of extent of disease, patients with lung cancer showed the lowest enzyme activity (mean 191 mU/ml +/- 30 SEM, P less than 0.001) and the greatest percent of weight loss (mean 16%), while patients with breast cancer had nearly normal lipase activity (mean 315 mU/ml +/- 50 SEM, normal 340 mU/ml +/- 22 SEM, P less than 0.10) and minimal weight loss (mean 8.4%). Fasting serum triglycerides were significantly elevated in the patient group (mean 120 mg/dl +/- 9.7 SEM) as compared to normal (mean 71 mg/dl +/- 7 SEM, P less than 0.001). The mean fasting insulin level was elevated in the patient group (13 mU/ml +/- 3.0 SEM), although in the majority of the patients it was found within the normal range (4-24 mU/ml). We conclude that the significant decrease in the total LPL activity may be responsible in part for the characteristic hypertriglyceridemia present in cancer patients.     

Changes of urinary steroid conjugates and gonadotropin excretion in the menstrual cycle and pregnancy in the Yunnan snub-nosed monkey (Rhinopithecus bieti).

The Yunnan snub-nosed monkey (Rhinopithecus bieti) is one of the most endangered species in the world, and it is endemic to China. According to our knowledge, there was no information on reproduction for this species. The present study was designed to understand the characteristics of reproductive hormone secretion during the menstrual cycle and pregnancy of this species by monitoring urinary estrone conjugate (E1C), pregnanediol-3-glucuronide (PdG), bioactive follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The urine samples were collected each day from four adult females for eight menstrual cycles, and once in 3 days during pregnancy (three full-term pregnancies, one mid-term abortion). The steroid conjugate was tested by radioimmunoassays (RIAs), and bioactive FSH and LH levels were measured in vitro by the sensitive bioassays granulosa cell aromatize bioassay (GAB) and rat interstitial cell testosterone (RICT), respectively. The results showed that: 1) E1C presented a preovulatory peak (183.9 +/- 8.6 ng/mgCr) followed by a definite elevation of PdG; 2) PdG in the luteal phase (754.4 +/- 30.6 ng/mgCr) was three- to fivefold higher than during the corresponding follicular phase (198.3 +/- 11.4 ng/mgCr); 3) the peaks of bio-LH and bio-FSH were on the same day, while the E1C peak was 1 or 2 days before the peaks for these two hormones; 4) bio-FSH levels were higher in the follicular phase than in the luteal phase, and bio-LH levels elevated slightly in the luteal phase; 5) the mean cycle length was 23.6 +/- 3.5 days (n = 3) based upon successive urinary LH peaks; 6) based on the interval from the day of E1C peak to the day of parturition, the gestation was 203.7 +/- 2.5 days (n = 3); and 7) both E1C and PdG increased and remained high after pregnancy, with a sharp decrease in basal levels following parturition or mid-term abortion. The results suggested that the pattern of reproductive hormones for R. bieti is similar to that of other Old World monkeys, but the concentration of the hormones is different from that of other species. This species has a longer progestation period, which may be related to its classification status.     

Steroid and gonadotropin hormone levels in young African women with filarial infection

Serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone (T), progesterone (P), estradiol (E2), prolactin (PRL), cortisol (F) and gonadotropins (FSH, LH) were analysed by radioimmunoassay for 125 schoolgirls aged 14-16, in a zone of endemic filariasis 3 days after menses. Two groups were identified: the infected group in which 38 subjects had circulating Loa loa and or Mansonella perstans microfilariae as determined by the Knott's concentration technique, and the non-infected group (87 subjects without microfilaremia). All results are expressed as the mean +/- SD. No significant difference was found between the two groups for age (14.47 +/- 1.37 yr vs 14.50 +/- 1.37 yr) or for body wt (46.10 +/- 8.45 kg vs 47.06 +/- 8.26 kg). There was a tendency to lower levels of DHEAS in the infected group by comparison with controls (54.92 +/- 37.34 micrograms/dl vs 66.80 +/- 47.18 micrograms/dl) while in the same infected group more subjects had higher levels of prolactin by comparison with the control group (10.85 +/- 14.16 ng/ml vs 9.80 +/- 5.56 ng/ml). Testosterone, progesterone, estradiol levels and the LH/FSH ratio were lower in the infected group than in the non-infected group (P: 0.25 +/- 0.12 ng/ml vs 0.33 +/- 0.20 ng/ml, P less than 0.025; T: 0.55 +/- 0.17 ng/ml vs 0.62 +/- 0.19 ng/ml, P less than 0.05; E2: 32.95 +/- 19.63 pg/ml vs 66.98 +/- 54.83 pg/ml, P less than 0.001; LH/FSH: 0.91 +/- 0.44 vs 1.30 +/- 0.84, P less than 0.005) respectively. No significant difference was found between the two groups for F; however FSH levels correlated negatively with F levels only in the microfilaremia group (r = -0.38, n = 38, P less than 0.05). Our results suggest that the presence of microfilaremia in our subjects may have contributed to reduced steroid levels, perhaps by involvement of the cyclic AMP kinase system. These observations may explain the delayed menarche and androgen secretion found during puberty in a similar population living in the same zone of endemic filariasis. Microfilaremia should therefore be considered an environmental factor which mediates endocrine disorders in subjects living in tropical filariasis areas.     

Phenotypic variation in testosterone and luteinizing hormone production among boars: differential response to gonadotropin releasing hormone and adrenocorticotropic hormone

Variation in ability of boars to produce testosterone and luteinizing hormone (LH) in response to both gonadotropin releasing hormone (GnRH) and adrenocorticotropic hormone (ACTH) stimulation, as well as quantitative relationships between pretreatment and posttreatment responses, were assessed in a population of 38 boars of similar age and breeding. Peripheral testosterone concentrations following either GnRH or ACTH increased (P less than 0.01) to peak circulating levels of 7.16 +/- 0.62 and 8.42 +/- 0.81 ng/ml by 120 and 45 min, respectively. Post-GnRH testosterone area varied from 7.44 to 50.84 ng/ml X h (CV = 47.44%) and post-ACTH testosterone area ranged from 3.05 to 28.78 ng/ml X h (CV = 46.09%). GnRH-induced increases in testosterone were preceded by elevations (P less than 0.01) in peripheral LH concentrations but ACTH had no effect upon LH levels. Post-GnRH area varied from 7.07 to 125.45 ng/ml X h (CV = 76.61%). Significant (P less than 0.01) correlations were obtained between pre-GnRH and post-GnRH testosterone areas (r = 0.58) and between pre-ACTH and post-ACTH testosterone areas (r = 0.67). Nonsignificant (P greater than 0.10) correlations were obtained between post-GnRH and post-ACTH testosterone areas (r = 0.006) and between post-GnRH testosterone and LH areas (r = 0.09). The testosterone producing ability of boars was highly variable and their innate ability to produce testosterone influenced their response to GnRH and ACTH. Additionally, the mechanisms by which GnRH and ACTH influence testosterone production in boars appear to differ. Variation in the ability of boars to produce testosterone could not be explained on the basis of differences in circulating levels of LH.